The thyroid gland, located in front of the windpipe, secretes the hormone thyroxine into the blood to regulate heart rate, body temperature and calorie consumption. When excess thyroid hormone is produced, a condition known as hyperthyroidism results.
Hyperthyroidism is usually caused by Graves' disease, a condition in which the body overproduces antibodies that specifically stimulate the thyroid gland. The majority of hyperthyroid patients are women. The typical patient becomes nervous, irritable, warm and has difficulty sleeping. The patient's skin is soft and velvety. Although appetite may increase, the patient still loses weight. Other symptoms include tremors, heavier periods and increased frequency of miscarriage. Fluid accumulation behind the eyeballs may move them forward, creating a wide-eyed appearance. Hyperthyroidism is lift-threatening if not treated.
There are presently three primary options for treating hyperthyroidism: 1) drug therapy to block production of thyroid hormones; 2) surgical removal of the thyroid gland; and 3) radioiodide treatment to permanently destroy thyroid gland function. A principal problem with either surgery or radioiodide treatment is that these procedures often cause irreversible hypothyroidism. Hypothyroidism, also known as myxedema, is a life-threatening disease state if untreated. Myxedema affects most major organ systems, for example, cardiovascular, renal, thermoregulation, digestion and respiratory. Since thyroid hormones play a vital role in normal cellular metabolism, treatment of hypothyroidism requires daily dosing of such patients with a pharmaceutical thyroid hormone preparation. Therefore, the more drastic and permanent therapies for hyperthyroidism are usually used only after drug therapy has been unsuccessfully tried or otherwise ruled out.
Drugs which inhibit the formation of thyroid hormones are usually administered orally. After taking the medicine for a few months to several years, about half the patients will exhibit remission of hyperthyroidism, 70 to 80% permanently. Wartofsky, L., McCall's, Nov. 1989, p.106. The primary advantage of anti-hyperthyroid drugs is that they do not cause permanent hypothyrodism and can be discontinued when remission of hyperthyroidism occurs. However, the anti-hypothyroid drugs typically cause permanent enzyme inactivation which can result in periods of hyperthyroidism after termination of drug therapy. The drugs which are most often used to treat hyperthyroidism are the thiourea derivatives propylthiouracil (PTU) and methimazole (MMI), both of which are available from Eli Lilly & Co.
There are two primary problems with anti-hyperthyroid drugs which are currently used today. The first problem is that PTU and MMI are "suicide" inhibitors of thyroid peroxidase (TPX) and the closely related model enzyme, lactoperoxidase (LPX). In this context, "suicide" means that once an enzyme molecule is inhibited by one of these drugs it is permanently inactivated. Thus, after three to four weeks of therapy, the doses of these anti-hyperthyroid drugs often require downward adjustment to prevent hypothyrodism.
A second problem with currently used anti-hyperthyroid drugs is their adverse side effects. Examples of side effects which are known to be caused by these drugs are skin rash, fever, arthralgias and life-threatening agranulocytosis. Cooper, D.S., Antithyroid drugs, The England Journal of Medicine, Vol.311, No. 21, Nov. 22, 1984 p. 1358.